Role of the liver in the degradation of very low density lipoproteins: a study of lipolysis by heparin releasable liver lipase and uptake during isolated rat liver perfusion.
The role of the liver and of a heparin-releasable liver lipase in the metabolism of very low density lipoprotein (VLDL) was investigated in vitro and during recycling rat liver perfusion. Rat plasma VLDL and nascent hepatic VLDL were labelled biosynthetically in their lipid moieties. Incubation in vitro of VLDL with the lipase caused hydrolysis of VLDL-triglycerides (greater than 80%) and VLDL-phosphatidylcholine (greater than 30%). Nascent VLDL was a better substrate for the enzyme. The hydrolytic activities were inhibited by 70--90% when rat plasma (10--30 vol%) was added to the incubation mixture. VLDL-triglycerides and cholesterol esters were taken up by the liver during 180 min recycling perfusion. The rate of disappearance of nascent VLDL was faster than that of plasma VLDL (half-life times of 56.2 +/- 13.9 and 125.0 +/- 24.8 min respectively). Injection of heparin into the perfusion medium caused accelerated uptake of the hydrolysed VLDL-triglyceride by the liver. Addition of plasma (d greater than 1.006 g/ml) to the perfusion at a concentration of 10 vol% delayed the rate of disappearance of VLDL from the perfusate by about 50--75%. These studies have established the capacity of the hepatic lipase to hydrolyse VLDL-lipids and the ability of the liver to degrade nascent and plasma VLDL particles. These two activities, however, are depressed by plasma and therefore previous studies of VLDL metabolism may have to be re-examined when based on incubations or perfusions in the absence of plasma.
D000818:Animals; D002474:Cell-Free System; D006493:Heparin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008049:Lipase / Q000378:metabolism*; D008066:Lipolysis; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism
D008079:Lipoproteins, VLDL; D010713:Phosphatidylcholines; D014280:Triglycerides; D012965:Sodium Chloride; D006493:Heparin; D008049:Lipase